The trial will evaluate the pharmacokinetics, safety, efficacy and acceptability of twice- and once-daily dosing of lopinavir/ritonavir tablets (Kaletra) dosed by weight in HIV-1 infected children who are currently taking lopinavir/ritonavir as part of their combination antiretroviral therapy and who are currently achieving virological suppression (<50 copies/ml). Specifically:

KONCERT A Kaletra ONCE Daily Randomised Trial of the Pharmacokinetics, Safety and Efficacy of Twice-daily Versus Once-daily Lopinavir/Ritonavir Tablets Dosed by Weight as Part of Combination Antiretroviral Therapy in Human Immunodeficiency Virus-1 (HIV-1) Infected Children (PENTA 18)

To evaluate whether once-daily dosing of lopinavir/ritonavir is comparable to twice-daily dosing in terms of virological suppression. This is measured by HIV-1 RNA ≥50 copies/ml (confirmed). [ Time Frame: week 48 ] [ Designated as safety issue: No ]

To evaluate whether once-daily dosing of lopinavir/ritonavir is comparable to twice-daily dosing in terms of virological suppression. This is measured by HIV-1 Ribonucleic acid (RNA) ≥50 copies/ml (confirmed).

To evaluate whether once-daily dosing of lopinavir/ritonavir is comparable to twice-daily dosing in terms of virological suppression. This is measured by HIV-1 RNA ≥50 copies/ml (confirmed). [ Time Frame: Week 36 ] [ Designated as safety issue: No ]

To evaluate whether once-daily dosing of lopinavir/ritonavir is comparable to twice-daily dosing in terms of virological suppression. This is measured by HIV-1 RNA ≥50 copies/ml (confirmed).

To evaluate whether once-daily dosing of lopinavir/ritonavir is comparable to twice-daily dosing in terms of virological suppression. This is measured by HIV-1 RNA ≥50 copies/ml (confirmed). [ Time Frame: week 24 ] [ Designated as safety issue: No ]

To evaluate whether once-daily dosing of lopinavir/ritonavir is comparable to twice-daily dosing in terms of virological suppression. This is measured by HIV-1 RNA ≥50 copies/ml (confirmed).

To evaluate whether once-daily dosing of lopinavir/ritonavir is comparable to twice-daily dosing in terms of virological suppression. This is measured by HIV-1 RNA ≥50 copies/ml (confirmed). [ Time Frame: week 12 ] [ Designated as safety issue: No ]

To evaluate whether once-daily dosing of lopinavir/ritonavir is comparable to twice-daily dosing in terms of virological suppression. This is measured by HIV-1 RNA ≥50 copies/ml (confirmed).

To evaluate whether once-daily dosing of lopinavir/ritonavir is comparable to twice-daily dosing in terms of virological suppression. This is measured by HIV-1 RNA ≥50 copies/ml (confirmed). [ Time Frame: week 8 ] [ Designated as safety issue: No ]

To evaluate whether once-daily dosing of lopinavir/ritonavir is comparable to twice-daily dosing in terms of virological suppression. This is measured by HIV-1 RNA ≥50 copies/ml (confirmed).

To evaluate whether once-daily dosing of lopinavir/ritonavir is comparable to twice-daily dosing in terms of virological suppression. This is measured by HIV-1 RNA ≥50 copies/ml (confirmed). [ Time Frame: week 4 ] [ Designated as safety issue: No ]

To evaluate whether once-daily dosing of lopinavir/ritonavir is comparable to twice-daily dosing in terms of virological suppression. This is measured by HIV-1 RNA ≥50 copies/ml (confirmed).

To compare the pharmacokinetics of twice-daily lopinavir/ritonavir tablets with once-daily dosing in the same children [ Time Frame: week 4 ] [ Designated as safety issue: No ]

Area under the curve (AUC), minimum observed plasma concentration (Cmin) and maximum observed plasma concentration (Cmax) values of lopinavir after once-daily and twice-daily dosing (in the same children)

Secondary Outcome Measures:

To evaluate whether once-daily dosing of lopinavir/ritonavir is comparable to twice-daily dosing in terms of virological suppression. This is measured by HIV-1 RNA <400/<50 copies/ml. [ Time Frame: week 24 ] [ Designated as safety issue: No ]

To evaluate whether once-daily dosing of lopinavir/ritonavir is comparable to twice-daily dosing in terms of virological suppression. This is measured by HIV-1 RNA <400/<50 copies/ml.

To evaluate whether once-daily dosing of lopinavir/ritonavir is comparable to twice-daily dosing in terms of virological suppression. This is measured by HIV-1 RNA <400/<50 copies/ml. [ Time Frame: week 48 ] [ Designated as safety issue: No ]

To evaluate whether once-daily dosing of lopinavir/ritonavir is comparable to twice-daily dosing in terms of virological suppression. This is measured by HIV-1 RNA <400/<50 copies/ml.

stable (i.e. CD4 not declining) on a combination antiretroviral regimen that has included lopinavir/ritonavir for at least 24 weeks

taking lopinavir/ritonavir dosed twice-daily and be willing at the screening visit to change to tablet formulation (if not currently taking tablets) and to change the lopinavir/ritonavir dose to follow the recommended FDA dosing plan based on body weight bands as necessary (see 7.2.2); if participating in the PK study*, be willing at the screening visit to change to lopinavir/ritonavir half strength formulation tablets (100/25mg) only, dosed twice-daily and change the lopinavir/ritonavir dose to follow the recommended FDA dosing plan based on body weight bands as necessary (see 7.2.1)

children and caregivers willing to participate in the PK study if they are among a minimum of the first 16 children enrolled in each body weight band in the trial, including a second PK assessment if randomised to switch to once-daily lopinavir/ritonavir.

parents/carers and children, where applicable, give informed written consent

Exclusion Criteria:

children on an antiretroviral regimen that includes a non-nucleoside reverse transcriptase inhibitor (NNRTI), fosamprenavir or nelfinavir

children who have previously failed virologically on a protease inhibitor (PI) containing regimen (where virological failure is defined as two successive HIV-1 RNA results>1000 copies/ml (confirmed) more than 24 weeks after starting highly active antiretroviral therapy (HAART), i.e changes for toxicity are not counted as failure)

acute illness

abnormal renal or liver function (grade 3 or above)

receiving concomitant therapy except for prophylaxis; Some treatments may be allowed, but must first be discussed with a trial medical expert

pregnancy or risk of pregnancy in females of child bearing potential

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01196195

Locations

Germany

Charite University Hospital Berlin

Berlin, Germany

Department of Pediatric Oncology Hematology and Immunology KA02

Dusseldorf, Germany

J W Goethe University

Frankfurt, Germany

Immundefekt-Ambulanz, Dr. von Haunersches Kinderspital

Munich, Germany

Ireland

Our Lady's Children's Hospital

Dublin, Ireland

Netherlands

Emma Childrens Hospital

Amsterdam, Netherlands

UMC St. Radboud

Nijmegen, Netherlands

Thailand

Program for HIV Prevention and Treatment (PHPT)/IRD 174

Changklan, Muang, Chiang Mai, Thailand, 50100

HIV-NAT Thai Red Cross AIDS Research Centre

Bangkok, Thailand

United Kingdom

Birmingham Heartlands Hospital

Birmingham, United Kingdom

University Hospital Bristol

Bristol, United Kingdom

Evelina Children's Hospital

London, United Kingdom

Great Ormond Street Hospital

London, United Kingdom

King's College Hospital

London, United Kingdom

St. Mary's Hospital

London, United Kingdom

Nottingham City Hospital Campus

Nottingham, United Kingdom

John Radcliffe Hospital

Oxford, United Kingdom

Sponsors and Collaborators

PENTA Foundation

Medical Research Council

French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)